Membrane-associated proteins and protein complexes account for −30% or more of the cellular proteins. Membrane proteins are held within a bilayer structure. The basic membrane bilayer construct consists of two opposing layers of amphiphilic molecules know as phospholipids; each molecule has a hydrophilic moiety, i.e., a polar phosphate group/derivative, and a hydrophobic moiety, i.e., a long hydrocarbon chain. These molecules self-assemble in a biological (largely aqueous) environment according to thermodynamics associated with water exclusion or hydrophobic association.
In order to facilitate the myriad functions of biological membranes including the passage of nutrients, signaling molecules and other molecules into and out of the cell, membrane proteins are arrayed in the bilayer structure. In particular, some proteins span the bilayer, others are anchored within the bilayer, and still others organize “peripheral” proteins into complexes. Many membrane bound protein complexes mediate essential cellular processes e.g. signal transduction, transport, recognition, and cell-cell communication.
In general, this class of proteins is challenging to study because of their insolubility and tendency to aggregate when removed from their protein lipid bilayer environment. Generally, although membrane proteins are optimally folded and functional when in a lipid bilayer, certain standard protein purification methods often remove lipids, invariably altering protein conformation and function.
Additionally, certain organisms, such as gram negative bacteria or plants, have membranes (e.g. outer membrane of gram negative bacteria), that are structurally different than the typical bilayer. Furthermore in gram negative bacteria, some membrane associated proteins span the inner membrane and outer membrane of the bacteria. Purification of membrane associated proteins from those organisms can be particularly challenging and many of those proteins often do not maintain their function following extraction.
The above challenges often make derivation and study of membrane proteins and membrane proteomes particularly difficult due to the complex structure and solubility of all the membrane proteins in a particular membrane fraction.